Molecular fundamentals of wound healing in diabetic foot syndrome;Molekulare grundlagen der wundheilung bei diabetischem fußsyndrom

Medizinische Klinik

Volumn 98, Issue 5, 2003, Pages 292-301

  Lobmann, Ralf ^a   Schultz, Gregory ^b   Lehnert, Hendrik ^a  

^a OTTO VON GUERICKE UNIVERSITY   (Germany)

^b UNIVERSITY OF FLORIDA   (United States)

Author keywords

Diabetic foot syndrome; Growth factors; Proteases; Wound healing

Indexed keywords

COLLAGENASE; CYTOKINE; GELATINASE; GROWTH FACTOR; INTERSTITIAL COLLAGENASE; PROTEINASE; STROMELYSIN; TISSUE INHIBITOR OF METALLOPROTEINASE;

DIABETES MELLITUS; DIABETIC FOOT; ENZYME ACTIVITY; HEALTH CARE; HUMAN; MEDICAL RESEARCH; PATHOGENESIS; PATHOPHYSIOLOGY; REVIEW; WOUND HEALING;

CHRONIC DISEASE; DIABETIC FOOT; ENDOPEPTIDASES; GENE EXPRESSION; GROWTH SUBSTANCES; HUMANS; WOUND HEALING;

EID: 0037612556     PISSN: 07235003     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00063-003-1260-2     Document Type: Review

References (159)

1. New JP, McDowell D, Burns E, Young RJ. Problem of amputations in patients with newly diagnosed diabetes mellitus. Diabet Med 1998;15:760-4.
2. Diabetes Care and Research Group in Europe. The Saint Vincent Declaration. Diabet Med 1990;7:360.
3. Trautner C, Haastert B, Spraul M, Giani G, Berger M. Unchanged incidence of lower-limb amputations in a German City, 1990-1998. Diabetes Care 2001; 24:855-9.
4. Trautner C, Haastert B, Giani G, Berger M. Amputations and diabetes: a case-control study. Diabet Med 2002;19:35-40.
5. Trautner C, Haastert B, Giani G, Berger M. Incidence of lower limb amputations and diabetes. Diabetes Care 1996;19:1006-9.
6. Standl E. Zur Epidemiologie des diabetischen Fußsyndroms. Diabetes Stoffw 2000;9:339-42.
7. Lobmann R. Ätiopathogenese und Diagnostik des diabetischen Fußsyndroms. Diabetes Stoffw 1999;8: Suppl 5:5-8.
8. Lobmann R. Konservative Therapie des diabetischen Fußes aus internistischer Sicht. Diabetes Stoffw 1999; 8:Suppl 5:9-11.
9. Hierl FX, Landgraf R. Clinical symptonzs and clinical diagnosis in diabetic foot syndrome. Internist (Berl) 1999;40:1002-8.
10. Landgraf R, Hierl FX. General therapy of patients with diabetic foot syndrome. Internist (Berl) 1999; 40:1018-23.
11. Spraul M, Hrsg. Internationaler Konsensus über den Diabetischen Fuß. Mainz: Kirchheim, 1999.
12. Edelson GW. Systemic and nutritional considerations in diabetic wound healing. Clin Podiatr Med Surg 1998:15:41-8.
13. Spravchikov N, Sizyakov G. Gartsbein M, Accili D, Tennenbaum T, Wertheimer E. Glucose effects on skin keratinocytes: implications for diabetes skin complications. Diabetes 2001:50:1627-35.
14. Nwomeh BC, Yager DR, Cohen IK. Physiology of the chronic wound. Clin Plast Surg 1998;25:341-56.
15. Lerman OZ, Galiano KD, Armour M, Levine JP, Gurtner GC. Cellular dysfunction in the diabetic fibroblast: impairment in migration, vascular endothelial growth factor production, and response to hypoxia. Am J Pathol 2003;162:303-12.
16. Hunt TK, Burke J, Barbul A, Gimbel ML. Wound healing. Science 1999;284:1775.
17. Mast BA, Schultz GS. Interactions of cytokines, growth factors and proteases in acute and chronic wounds. Wound Repair Regen 1996;4:411-20.
18. Tamuzzer RW, MacAuley S, Bruce M, et al. Epidermal growth factor in wound healing: a model for molecular pathogenesis of chronic wounds. In: Ziegler TR Pierce GF, Herndon DN, ed. Growth factors and wound healing. Basic science and potential clinical apllications. Serono Symposia. Norwell: Serono, 1995.
19. Tarnuzzer RW, Schultz GS. Biochemical analysis of acute and chronic wound environments. Wound Repair Regen 1996;4:321-5.
20. Lazarus GS, Cooper DM, Knighton DR, Margolis DJ, Pecoraro RE, Rodeheaver G, Robson MC. Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol 1994;130: 489-93.
21. Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med 1999;341:738-46.
22. Gillitzer R, Goebeler M. Chemokines in cutaneous wound healing. J Leukoc Biol 2001;69:513-21.
23. Ravanti L, Kahari VM. Matrix metalloproteinases in wound repair [Review]. Int J Mol Med 2000;6: 391-407.
24. Cohen IK, Mast BA. Models of wound healing. J Trauma 1990;30:S149-55.
25. Lynch SE, Colvin RB, Antoniades HN. Growth factors in wound healing. Single and synergistic effects on partial thickness porcine skin wounds. J Clin Invest 1989:84:640-6.
26. Yager DR, Zhang Y, Liang H-X, Diegelmann RF, Cohen IK. Wound fluids from human pressure ulcers contain elevated matrix metalloproteinase levels and activity compared to surgical wound fluids. J Invest Dermatol 1996;107:743-8.
27. Chen C, Schultz GS, Bloch M, Edwards PD, Tebes S, Mast BA. Molecular and mechanistic validation of delayed healing rat wounds as a model for human chronic wounds. Wound Repair Pegen 1999:7:486-94.
28. Trengove NJ, Stacey MC, MacAuley S, Bennett N, Gibson J, Burslem F, Murphy G, Schultz G. Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors. Wound Repair Regen 1999;7:442-52.
29. Trengove NJ, Bielefeldt-Ohmann H, Stacey MC. Mitogenic activity and cytokine levels in non-healing and healing chronic leg ulcers. Wound Repair Regen 2000;8:13-25.
30. Cooper DM, Yu EZ, Hennessey PJ, Ko F, Robson MC. Determination of endogenous cytokines in chronic wounds. Ann Surg 1994;219:688-92.
31. Katz MH, Alvarez AF, Kirsner RS, Eaglstein WH, Falanga V. Human wound fluid from acute wounds stimulates fibroblast and endothelial cell growth. J Am Acad Dermatol 1991;25:1054-8.
32. Falanga V. Growth factors and chronic wounds: the need to understand the microenvironment. J Dermatol 1992;19:667-72.
33. Bennett NT, Schultz GS. Growth factors and wound healing: part II. Role in normal and chronic wound healing. Am J Surg 1993;166:74-81.
34. Alheim K, Bartfai T. The interleukin-1 system: receptors, ligands, and ICE in the brain and their involvement in the fever response. Ann N Y Acad Sci 1998;840:51-8.
35. Graves DT, Nooh N, Gillen T, Davey M, Patel S, Cottrell D, Amar S. IL-1 plays a critical role in oral, but not dermal, wound healing. J Immunol 2001;167: 5316-20.
36. Sauder DN, Kilian PL, McLane JA, Quick TW, Jakubovic H, Davis SC, Eaglstein WH, Mertz PM. Interleukin-1 enhances epidermal wound healing. Lymphokine Res 1990;9:465-73.
37. Barbul A, Knud-Hansen J, Wasserkrug HL, Efron G. Interleukin 2 enhances wound healing in rats. J Surg Res 1986;40:315-9.
38. Barbul A. Role of T-cell-dependent immune system in wound healing. Prog Clin Biol Res 1988;266: 161-75.
39. Mustoe TA, Pierce GF, Thomason A, Gramates P, Sporn MB, Deuel TF. Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta. Science 1987;237:1333-6.
40. Deuel TF, Kawahara RS, Mustoe TA, Pierce AF. Growth factors and wound healing: platelet-derived growth factor as a model cytokine. Annu Rev Med 1991;42:567-84.
41. Ross R. Platelet-derived growth factor. Lancet 1989; 8648:1179-82.
42. Beer HD, Longaker MT, Werner S. Reduced expression of PDGF and PDGF receptors during impaired wound healing. J Invest Dermatol 1997;109:132-8.
43. Kähäri V-M, Saarialho-Kere UK. Matrix metalloproteinases in skin. Exp Dermatol 1997;6:199-213.
44. Woessner JF Jr. The family of matrix metalloproteinases. Ann N Y Acad Sci 1994;732:11-21.
45. Kerkela E, Ala-aho K, Lohi J, Grenman R, Kahari V, Saarialho-Kere U. Differential patterns of stromelysin-2 (MMP-10) and MT1-MMP (MMP-14) expression in epithelial skin cancers. Br J Cancer 2001:84:659-69.
46. Laack E, Kohler A, Kugler C, Dierlamm T, Knuffmann C, Vohwinkel G, Niestroy A, Dahlmann N, Peters A, Berger J, Fiedler W, Hossfeld DK. Pretreatment serum levels of matrix metalloproteinase-9 and vascular endothelial growth factor in non-small-cell lung cancer. Ann Oncol 2002;13:1550-7.
47. Kugler A. Matrix metalloproteinases and their inhibitors. Anticancer Res 1999;19:1589-92.
48. John A, Tuszynski G. The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis. Pathol Oncol Res 2001;7:14-23.
49. Mengshol JA, Mix KS, Brinckerhoff CE. Matrix metalloproteinases as therapeutic targets in arthritic diseases: bull's-eye or missing the mark? Arthritis Rheum 2002;46:13-20.
50. Constantin A, Lauwers-Cances V, Navaux F, Abbal M, van Meerwijk J, Mazieres B, Cambon-Thomsen A, Cantagrel A. Stromelysin 1 (matrix metalloproteinase 3) and HLA-DRB1 gene polymorphisms: association with severity and progression of rheumatoid arthritis in a prospective study. Arthntis Rheum 2002;46:1754-62.
51. Itoh T, Matsuda H, Tanioka M, Kuwabara K, Itohara S, Suzuki R. The role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in antibody-induced arthritis. J Immunol 2002;169:2643-7.
52. Parks WC, Shapiro SD. Matrix metalloproteinases in lung biology. Respir Res 2001;2:10-9.
53. Zheng T, Zhu Z, Wang Z, Homer RJ, Ma B, Riese RJ Jr, Chapman HA Jr, Shapiro SD, Ellas JA. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema. J Clin Invest 2000;106:1081-93.
54. Shapiro SD. Elastolytic metalloproteinases produced by human mononuclear phagocytes. Potential roles in destructive lung disease. Am J Respir Crit Care Med 1994;150: S160-4.
55. Nwomeh BC, Liang HX, Diegelmann RF, Cohen IK, Yager DR. Dynamics of the matrix metalloproteinases MMP-1 and MMP-8 in acute open human dermal wounds. Wound Repair Regen 1998;6:127-34.
56. Parsons SL, Watson SA, Brown PD, Collins HM, Steele JC. Matrix metalloproteinase. Br J Surg 1997; 84:160-6.
57. Han YP, Tuan TL, Wu H, Hughes M, Garner WL. TNF-alpha stimulates activation of pro-MMP2 in human skin through NF-(kappa)B mediated induction of MT1-MMP. J Cell Sci 2001; 114:131-9.
58. Armstrong DG, Jude EB. The role of matrix metalloproteinases in wound healing. J Am Pediatr Med Assoc 2002;92:12-8.
59. Van Wart HE, Birkedal-Hansen H. The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proc Natl Acad Sci U S A 1990;87:5578-82.
60. Murphy G. Matrix metalloproteinases and their inhibitors. Acta Orthop Scand Suppl 1995;266:55-60.
61. Murphy G, Willenbrock F. Tissue inhibitors of matrix metalloendopeptidases. Methods Enzymol 1995;248: 496-510.
62. DeClerck YA, Yean TD, Lu HS, Ting J, Langley KE. Inhibition of autoproteolytic activation of interstitial procollagenase by recombinant metalloproteinase inhibitor MI/TIMP-2. J Biol Chem 1991;266:3893-9.
63. Mauviel A. Cytokine regulation of metalloproteinase gene expression. J Cell Biochem 1993;53:288-95.
64. Zhang Y, McCluskey K, Fujii K, Wahl LM. Differential regulation of monocyte matrix metalloproteinase and TIMP-1 production by TNF-α, granulocytemacrophage CSF, and IL-lb through prostaglandindependent and independent mechanism. J Immunol 1998;161:3071-6.
65. McCawley LJ, O'Brien P, Hudson LG. Epidermal growth factor (EGF)- and scatter factor/hepatocyte growth factor (SF/HGF)-mediated keratinocyte migration is coincident with induction of matrix metalloproteinase (MMP)-9. J Cell Physiol 1998;176: 255-65.
66. Li DQ, Lokeshwar BL, Solomon A, Monroy D, Ji Z, Pflugfelder SC. Regulation of MMP-9 production by human corneal epithelial cells. Exp Eye Res 2001; 73:449-59.
67. Bond M, Baker AH, Newby AC. Nuclear factor kappaB activity is essential for matrix metalloproteinase-1 and -3 upregulation in rabbit dermal fibroblasts. Biochem Biophys Res Commun 1999;264:561-7.
68. Mauviel A, Chung KY, Agarwal A, Tamai K, Uitto J. Cell-specific induction of distinct oncogenes of the Jun family is responsible for differential regulation of collagenase gene expression by transforming growth factor-beta in fibroblasts and keratinocytes. J Biol Chem 1996;271:10917-23.
69. Kim JH, Hong SH, Nah HY, Lee JY, Chae HD, Kim CH, Kang BM, Bae IH. Influence of transforming growth factor-alpha on expression of matrix metalloproteinase-2, matrix metalloproteinase-9, and epidermal growth factor receptor gene in the mouse blastocysts. J Assist Reprod Genet 2002;19:232-9.
70. Han YP, Tuan TL, Hughes M, Wu H, Gamer WL. Transforming growth factor-beta- and tumor necrosis factor-alpha-mediated induction and proteolytic activation of MMP-9 in human skin. J Biol Chem 2001;276:22341-50.
71. Johansson N, Westermarck J, Leppa S, Hakkinen L, Koivisto L, Lopez-Otin C, Peltonen J, Heino J, Kahari VM. Collagenase 3 (matrix metalloproteinase 13) gene expression by HaCaT keratinocytes is enhanced by tumor necrosis factor alpha and transforming growth factor beta. Cell Growth Differ 1997;8:243-50.
72. Schroen DJ, Brinckerhoff CE. Nuclear hormone receptors inhibit matrix metalloproteinase (MMP) gene expression through diverse mechanisms. Gene Expr 1996;6:197-207.
73. Birkedal-Hansen H. Proteolytic remodeling of extracellular matrix. Curr Opin Cell Biol 1995;7:728-35.
74. Nwomeh BC, Liang H-X, Cohen IK, Yager DR. MMP-8 is the predominant collagenase in healing wounds and nonhealing ulcers. J Surg Res 2001; 81:189-95.
75. Borregaard N, Kjeldsen L, Lollike K, Sengelov H. Granules and vesicles of human neutrophils. The role of endomembranes as source of plasma membrane proteins. Eur J Haematol 1993;51:318-22.
76. Arumugam S, Jang YC, Chen-Jensen C, Gibran NS, Isik FF. Temporal activity of plasminogen activators and matrix metalloproteinases during cutaneous wound repair. Surgery 1999;125:587-93.
77. Agren MS. Gelatinase activity during wound healing. Br J Dermatol 1994;131:634-40.
78. Pilcher BK, Wang M, Qin XJ, Parks WC, Senior RM, Welgus HG. Role of matrix metalloproteinases and their inhibition in cutaneous wound healing and allergic contact hypersensitivity. Ann N Y Acad Sci 1999; 878:12-24.
79. Murphy GJ, Murphy G, Reynolds JJ. The origin of matrix metalloproteinases and their familial relationships. FEBS Lett 1991;289:4-7.
80. McDonnell S, Matnsian LM. Stromelysin in tumor progression and metastasis. Cancer Metastasis Rev 1990;9:305-19.
81. Young PJ, Grinnell F. Metalloproteinase activation cascade after burn injury: a longitudinal analysis of the human wound environment. J Invest Dermatol 1994;103:660-4.
82. Seiki M. Membrane-type matrix metalloproteinases. APMIS 1999;107:137-43.
83. Ueno H, Nakamura H, Inoue M, Imai K, Noguchi M, Sato H, Seiki M, Okada Y. Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in human invasive breast carcinomas. Cancer Res 1997;57:2055-60.
84. Pei D, Weiss SJ. Transmembrane-deletion mutants of the membrane-type matrix metalloproteinase-1 process progelatinase A and express intrinsic matrixdegrading activity. J Biol Chem 1996;271:9135-40.
85. DeClerck YA, Yean TD, Lee Y, Tomich JM, Langley KE. Characterization of the functional domain of tissue inhibitor of metalloproteinases-2 (TIMP-2). Biochem J 1993;289:65-9.
86. Goldberg GI, Marmer BL, Grant GA, Eisen AZ, Wilhelm S, He CS. Human 72-kilodalton type IV collagenase forms a complex with a tissue inhibitor of metalloproteases designated TIMP-2. Proc Natl Acad Sci U S A 1989;86:8207-11.
87. Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 2000;1477: 267-83
88. Madlener M, Parks WC, Werner S. Matrix metalloproteinases (MMPs) and their physiological inhibitors (TIMPs) are differentially expressed during excisional skin wound repair. Exp Cell Res 1998;242:201-10.
89. Saarialho-Kere UK. Patterns of matrix metalloproteinase and TIMP expression in chronic ulcers. Arch Dermatol Res 1998;290:Suppl:S47-54.
90. Vaalamo M, Weckroth M, Puolakkainen P, Kere J, Saarinen P, Lauharanta J, Saarialho-Kere UK. Patterns of matrix metalloproteinase and TIMP-1 expression in chronic and normally healing human cutaneous wounds. Br J Dermatol 1996;135:52-9.
91. Wang JF, Olson ME, Reno CR, Kulyk W, Wright JB, Hart DA. Molecular and cell biology of skin wound healing in a pig model. Connect Tissue Res 2000;41:195-211.
92. Mun-Bryce S, Rosenberg GA. Gelatinase B modulates selective opening of the blood-brain barrier during inflammation. Am J Physiol 1998;274:R1203-11.
93. Zhang H, Li C, Baciu PC. Expression of integrins and MMPs during alkaline-burn-induced corneal angiogenesis. Invest Ophthalmol Vis Sci 2002;43:955-62.
94. Stricklin GP, Li L, Jancic V, Wenczak BA, Nanney LB. Localization of mRNAs representing collagenase and TIMP in sections of healing human burn wounds. Am J Pathol 1993; 143:1657-66.
95. Ladwig GP, Robson MC, Liu R, Kuhn MA, Muir DF, Schultz GS. Ratios of activated matrix metalloproteinase-9 to tissue inhibitor of matrix metalloproteinase-1 in wound fluids are inversely correlated with healing of pressure ulcers. Wound Repair Regen 2002;10:26-37.
96. Saarialho-Kere UK, Pentland AP, Birkedal-Hansen H, Parks WC, Welgus HG. Distinct populations of basal keratinocytes express stromelysin-1 and stromelysin-2 in chronic wounds. J Clin Invest 1994;94:79-88.
97. Porras-Reyes BH, Blair HC, Jeffrey JJ, Mustoe TA. Collagenase production at the border of granulation tissue in a healing wound: macrophage and mesenchymal collagenase production in vivo. Connect Tissue Res 1991;27:63-71.
98. Vaalamo M, Leivo T, Saanalho-Kere U. Differential expression of tissue inhibitors of metalloproteinases (TIMP-1, -2, -3, and -4) in normal and aberrant wound healing. Hum Pathol 1999;30:795-802.
99. Bullen EC, Longaker MT, Updike DL, Benton R, Ladin D, Hou Z, Howard EW. Tissue inhibitor of metalloproteinases-1 is decreased and activated gelatinases are increased in chronic wounds. J Invest Dermatol 1995;104:236-40.
100. Wysocki AB, Staiano-Coico L, Grinnell F. Wound fluid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9. J Invest Dermatol 1993;101:64-8.
101. Vaalamo M, Mattila L, Johansson N, et al. Distinct populations of stromal cells express collagenase-3 (MMP-13) and collagenase-1 (MMP-1) in chronic ulcers but not in normally healing wounds. J Invest Dermatol 1997;109:96-101.
102. Salo T, Makela M, Kylmaniemi M, Autio-Harmainen H, Larjava H. Expression of matrix metalloproteinase-2 and -9 during early human wound healing. Lab Invest 1994;70:176-82.
103. Weckroth M, Vaheri A, Lauharanta J, Sorsa T, Konttinen YT. Matrix metalloproteinases, gelatinase and collagenase, in chronic leg ulcers. J Invest Dermatol 1996;106:1119-24.
104. Soo C, Shaw WW, Zhang X, Longaker MT, Howard EW, Ting K. Differential expression of matrix metalloproteinases and their tissue-derived inhibitors in cutaneous wound repair. Plast Reconstr Surg 2000;105:638-47.
105. Loots MA, Lamme EN, Zeegelaar J, Mekkes JR, Bos JD, Middelkoop E. Differences in cellular infiltrate and extracellular matrix ofchronic diabetic and venous ulcers versus acute wounds. J Invest Dermatol 1998;111:850-7.
106. Dahn MS. The role of growth factors in wound management of diabetic foot ulcers. Federal Practitioner 1998;7:14-9.
107. Mansbridge JN, Liu K, Pinney RE, Patch R, Ratcliffe A, Naughton GK. Growth factors secreted by fibroblasts: role in healing diabetic foot ulcers. Diabetes Obes Metab 1999;1:265-79.
108. Davidson JM, Broadley KN, Quaglino D Jr. Reversal of the wound healing deficit in diabetic rats by recombined basic fibroblast growth factor and transforming growth factor-b1 therapy. Wound Repair Regen 1997;5:77.
109. Puolakkainen PA, Twardzik DR, Ranchalis JE, Pankey SC, Reed MJ, Gombotz WR. The enhancement in wound healing by transforming growth factor-beta 1 (TGF-beta 1) depends on the topical delivery system. J Surg Res 1995;58:321-9.
110. Knighton DR, Ciresi K, Fiegel VD, Austin LL, Butler E. Classification and treatment of chronic, nonhealing wounds: successful treatment with autologous platelat-derived wound healing factors (PDWHF). Ann Surg 1986;204:322-30.
111. Wieman TJ. Clinical efficacy of becaplermin (rh-PDGF-BB) gel. Becaplermin Gel Studies Group. Am J Surg 1998;176:2A Suppl:74S-9S.
112. Loot MA, Kenter SB, Au FL, van Galen WJ, Middelkoop E, Bos JD, Mekkes JR. Fibroblasts derived from chronic diabetic ulcers differ in their response to stimulation with EGF, IGF-I, bFGF and PDGF-AB compared to controls. Eur J Cell Biol 2002;81: 153-60.
113. Greenhalgh DG, Sprugel KH, Murray MJ, Ross R. PDGF and FGF stimulate wound healing in the genetically diabetic mouse. Am J Pathol 1990;136: 1235-46.
114. Holloway GA, Steed DL, DeMarco MJ, Masumoto T, Moosa HH, Webster MW, Bunt TJ, Polansky M. A randomized, controlled, multicenter, dose response trial ofactivated platelet supernatent, topical CT-102 in chronic, non-healing, diabetic wounds. Wounds 1993;5:198-206.
115. Ladin D. Becaplermin gel (PDGF-BB) as topical wound therapy. Plastic Surgery Educational Foundation DATA Committee. Plast Reconstr Surg 2000;105:1230-1.
116. Mandracchia VJ, Sanders SM, Frerichs JA. The use of becaplermin (rhPDGF-BB) gel for chronic nonhealing ulcers. A retrospective analysis. Clin Podiatr Med Surg 2001;18:189-209.
117. Pierce GF, Tarpley JE, Tseng J, Bready J, Chang D, Kennedy WC, Ross R, Robson MC, Berg JV, Reid P, Kaufman S, Farrell CL. Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF in chronic nonhealing wounds. J Clin Invest 1995; 96:1336-50.
118. Robson MC, Phillips LG, Thomason A, Robson LE, Pierce GF. Platelet-derived growth factor BB for the treatment of chronic ulcers. Lancet 1992;339:23-5.
119. Smiell JM. Clinical safety of becaplermin (rhPDGF-BB) gel. Becaplermin Studies Group. Am J Surg 1998;176:2A Suppl:68S-73S.
120. Smiell J, Wieman TJ, Steed DL, Perry BH, Sampson AR, Schwab BH. Efficacy and safety of becaplermin (recombinant human platelet-derived growth factor-BB) in patients with non-healing, lower extremity diabetic ulcers: a combined analysis of four randomized studies. Wound Repair Regen 1999;7:335-46.
121. Lee HM, Golub LM, Chan D, Leung M, Schroeder K, Wolff M, Simon S, Crout R. alpha 1-proteinase inhibitor in gingival crevicular fluid of humans with adult periodontitis: serpinolytic inhibition by doxycycline. J Periodontal Res 1997;32:9-19.
122. Lamparter S, Slight SH, Weber KT. Doxycycline and tissue repair in rats. J Lab Clin Med 2002;139: 295-302.
123. Lauhio A, Konttinen YT, Tschesche H, Nordstrom D, Salo T, Lahdevirta J, Golub LM, Sorsa T. Reducdon of matrix metalloproteinase 8-neutrophil collagenase levels during long-term doxycycline treatment of reactive arthritis. Antimicrob Agents Chemother 1994;38:400-2.
124. Pirila E, Parikka M, Ramamurthy NS, Maisi P, McClain S, Kucine A, Tervahartiala T, Prikk K, Golub LM, Salo T, Sorsa T. Chemically modified terracycline (CMT-8) and estrogen promote wound healing in ovariectomized rats: effects on matrix metalloproteinase-2, membrane type 1 matrix metalloproteinase, and laminin-5 gamma2-chain. Wound Repair Regen 2002;10:38-51.
125. Cullen B, Smith R, McCulloch E, Silcock D, Morrison L. Mechanism ofaction of PROMOGRAN, a protease modulating matrix, for the treatment of diabetic foot ulcers. Wound Repair Regen 2002; 10:16-25.
126. Ghamekar O, Willis M, Persson U. Cost-effectiveness of creating deep diabetic foot ulcers with Promogran in four European countries. J Wound Care 2002;11:70-4.
127. Veves A, Sheehan P, Pham HT. A randomized, controlled trial of Promogran (a collagen/oxidized regenerated cellulose dressing) vs standard treatment in the management of diabetic foot ulcers. Arch Surg 2002;137:822-7.
128. Vin F, Teot L, Meaume S. The healing properties of promogran in venous leg ulcers. J Wound Care 2002;11:335-41.
129. Greenway SE, Filler LE, Greenway FL. Topical insulin in wound healing: a randomised, double-blind, placebo-controlled trial. J Wound Care 1999;8: 526-8.
130. Embil JM, Papp K, Sibbald G, Tousignant J, Smiell JM, Wong B, Lau CY. Recombinant human platelet-derived growth factor-BB (becaplermin) for healing chronic lower extremity diabetic ulcers: an open-label clinical evaluation of efficacy. Wound Repair Regen 2000; 8:162-8.
131. Fu X, Shen Z, Guo Z, Zhang M, Sheng Z. Healing of chronic cutaneous wounds by topical treatment with basic fibroblast growth factor. Chin Med J (Engl) 2002;115:331-5.
132. Quaghno D Jr, Nanney LB, Kennedy R, Davidson JM. Transforming growth factor-beta stimulates wound healing and modulates extracellular matrix gene expression in pig skin. 1. Excisional wound model. Lab Invest 1990;63:307-19.
133. Payne WG, Ochs DE, Meltzer DD, Hill DP, Mannan RJ, Robson LE, Robson MC. Long-term outcome study of growth factor-treated pressure ulcers. Am J Surg 2001;181:81-6.
134. Yager DR, Nwomeh BC. The proteolytic environment of chronic wounds. Wound Repair Regen 1999;7:433-41.
135. Lobmann R, Ambrosch A, Schultz G, Waldmann K, Schiweck S, Lehnert H. Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients. Diabetologia 2002; 45:1011-6.
136. Falanga V. Wound healing and chronic wounds. J Cutan Med Surg 1998;3:Suppl 1:S1-5.
137. Baker EA, Leaper DJ. Proteinases, their inhibitors, and cytokine profiles in acute wound fluid. Wound Repair Regen 2000;8:392-8.
138. Madlener M. Differential expression of matrix metalloproteinases and their physiological inhibitors in acute murine skin wounds. Arch Dermatol Res 1998;290:Suppl:S24-9.
139. Ottino P, Taheri F, Bazan HE. Platelet-activating factor induces the gene expression of TIMP-1, -2, and PAI-1: imbalance between the gene expression of MMP-9 and TIMP-1 and -2. Exp Eye Res 2002;74:393-402.
140. Williams RE, Armstrong DG. Wound healing. New modalities for a new millennium. Clin Podiatr Med Surg 1998;15:117-28.
141. Knighton DR, Ciresi K, Fiegel VD, Schumerth S, Butler E, Cerra F. Stimulation of repair in chronic nonhealing cutaneous ulcers using platelet-derived wound healing formula. Surg Gynecol Obstet 1990;170:56-60.
142. Knighton DR, Fiegel VD. Growth factors and comprehensive surgical care of diabetic wounds. Curr Opin Gen Surg 1993:32-9.
143. Robson MC, Mustoe TA, Hunt TK. The future of recombinant growth factors in wound healing. Am J Surg 1998;176:80S-2S.
144. Steed DL. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. Diabetic Ulcer Study Group. J Vasc Surg 1995;21:71-8.
145. Smith GN Jr, Mickler EA, Hasty KA, Brandt KD. Specificity of inhibition of matrix metalloproteinase activity by doxycycline: relationship to structure of the enzyme. Arthritis Rheum 1999;42:1140-6.
146. Brantigan CO. The history of understanding the role of growth factors in wound healing. Wounds 1996;8:78-90.
147. Woessner JF Jr. Matrix metalloproteinase inhibition. From the Jurassic to the third millennium. Ann N Y Acad Sci 1999;878:388-403.
148. Abbott CA, Vileikyte L, Williamson S, Carrington AL, Boulton AJ. Multicenter study of the incidence of and predictive risk factors for diabetic neuropathic foot ulceration. Diabetes Care 1998; 21:1071-5.
149. Ahroni JH. Preventing diabetic foot complications. Adv Skin Wound Care 2000;13:38-9.
150. Ahroni JH. Tool chest: teaching foot care creatively and successfully. Diabetes Educator 1993;19:320-4.
151. Culleton JL. Preventing diabetic foot foot complications. Tight glucose control and patient education are the keys. Postgrad Med 1999;106:74-8, 83.
152. McConnell EA. Teaching a patient with diabetes how to protect her feet. Nursing 1998;28:32.
153. Meijer JW, Links TP, Smit AJ, Groothoff JW, Eisma WH. Evaluation of a screening and prevention programme for diabetic foot complications. Prosthet Orthot Int 2001;25:132-8.
154. Peter-Riesch B, Assal J-P. Teaching diabetic foot care effectively. J Am Podiatr Med Assoc 1997; 87:318-20.
155. Apelqvist J, Larsson J. What is the most effective way to reduce incidence of amputation in the diabetic foot? Diabetes Metab Res Rev 2000;16:Suppl 1:S75-83.
156. Levin ME. Prevention and treatment of diabetic foot wounds. J Wound Ostomy Continence Nurs 1998; 25:129-46.
157. Oyibo SO, Jude EB, Tarawneh I, Nguyen HC, Harkless LB, Boulton AJ. A comparison of two diabetic foot ulcer classification systems: the Wagner and the University of Texas wound classification systems. Diabetes Care 2001;24:84-8.
158. Steed DL, Donohoe D, Webster MW, Lindsley L. Effect of extensive debridement and treatment on the healing of diabetic foot ulcers. J Am Coll Cardiol 1996;183:61-4.
159. Steed DL. Foundation of good ulcer care. Am J Surg 1998;176:20S-5S.